Feasibility Study of Intraperitoneal Paclitaxel
Primary Purpose
Gastric Cancer
Status
Unknown status
Phase
Phase 2
Locations
Singapore
Study Type
Interventional
Intervention
IP Paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Gastric Cancer focused on measuring Advanced gastric cancer, unresectable gastric cancer, recurrent gastric cancer, with peritoneal metastasis, cancer cells on peritoneal cytology
Eligibility Criteria
Inclusion Criteria:
- Histologically proven unresectable or recurrent adenocarcinoma of stomach and gastroesophageal junction
- Patients without prior systemic treatment. Patients who completed postoperative adjuvant chemotherapy (and radiotherapy) more than 180 days before may be enrolled
- Peritoneal metastasis and/or cancer cells on peritoneal cytology
- Age >21 years
- Eastern Cooperative Oncology Group performance status 0-2
- Adequate bone marrow function (neutrophil count >1500/mm3, hemoglobin >8.0 g/dl and platelet count >100 000/mm3)
- Adequate liver function (bilirubin, AST (aspartate aminotransferase)/ALT (alanine aminotransferase) within upper limit of normal)
- Adequate renal function (serum creatinine within the upper limit of normal)
- Expected survival >3 months
- Able to take orally
- Able to understand and the willingness to sign a written informed consent document
- The effects of proposed regimen on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because antitumor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Exclusion Criteria:
- Metastasis to distant organ sites (such as the liver, lungs or bone)
- When trastuzumab is considered for palliative chemotherapy
- Known allergy to taxane, fluoropyrimidine or oxaliplatin
- Previous malignancy other than gastric cancer diagnosed in the last 5 years except for basal cell carcinoma of skin or preinvasive cancer of cervix
- Patients with reproductive potential who refuse to use an adequate means of contraception (including male patients)
- Significant disease or conditions which, in the investigator's opinion, would exclude patient from the study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or lactating female
Sites / Locations
- National University HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
IP Paclitaxel
Arm Description
Paclitaxel will be administered intraperitoneally at 40mg/m2 on Days 1 and 8 in a 21-day cycle in patients receiving intravenous oxaliplatin 100mg/m2 on Day 1 and capecitabine 1000mg/m2 twice daily on Days 1-14.
Outcomes
Primary Outcome Measures
Overall survival (OS) rate
The primary end point is 1-year survival because most patients may not have measurable disease, hence response rate and progression free survival are less easy to assess.
Secondary Outcome Measures
Number of participants with adverse events
Toxicity will be monitored 3-weekly and graded according to the National Cancer Institute -Common Terminology Criteria for Adverse Events version 4.0.
Full Information
NCT ID
NCT01739894
First Posted
October 15, 2012
Last Updated
June 6, 2016
Sponsor
National University Hospital, Singapore
1. Study Identification
Unique Protocol Identification Number
NCT01739894
Brief Title
Feasibility Study of Intraperitoneal Paclitaxel
Official Title
Feasibility Study of Intraperitoneal Paclitaxel With Oxaliplatin and Capecitabine in Patients With Advanced Gastric Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Unknown status
Study Start Date
January 2013 (undefined)
Primary Completion Date
November 2017 (Anticipated)
Study Completion Date
August 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National University Hospital, Singapore
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single arm phase 2 trial evaluating the efficacy and tolerability of intraperitoneal paclitaxel with oxaliplatin and capecitabine in advanced gastric cancer patients with peritoneal metastasis and/or cancer cells on peritoneal cytology. Twenty patients will be recruited into the study for an estimated period of two years. Paclitaxel will be administered intraperitoneally at 40mg/m2 on Day 1 and 8 in patients receiving standard intravenous oxaliplatin 130mg/m2 on Day 1 and capecitabine 1000mg/m2 on day 1-14. The study hypothesizes that the addition of intraperitoneal paclitaxel with chemotherapy will improve treatment efficacy.
Detailed Description
The median survival of patients with unresectable gastric cancer treated with systemic chemotherapy is about 12 months. In patients with histologically proven unresectable or recurrent gastric cancer limited to the peritoneum and/or cancer cells in peritoneal cytology, the combination of i.p. paclitaxel with systemic chemotherapy reported a median survival time of 23.6 months. The peritoneal cytology turned negative for 86% of patients. In an updated report, gastrectomy was performed on 52 patients after disappearance or obvious shrinkage of peritoneal metastasis. In this cohort, the median survival time (MST) was 34.9 months. A phase III trial (PHOENIX-GC trial (Phase III study of S-1 plus intravenous and intraperitoneal paclitaxel versus S-1 plus cisplatin for gastric cancer with peritoneal metastasis )) comparing intraperitoneal(IP) regimen with systemic chemotherapy versus systemic therapy alone is currently opened for recruitment in Japan.
The multidisciplinary treatment combining IP-containing chemotherapy and surgery was found to be safe and effective for gastric cancer patients with peritoneal metastasis. A phase I study combining i.p. paclitaxel with oxaliplatin and S-1, found no dose limiting toxicity in all dose levels. Grade 3 neutropenia was observed in one patient at recommended phase 2 dose (RP2D) of i.p. paclitaxel of 40 mg/m2. In addition, grade 2 non-hematological toxicities observed were anorexia (n=6/12), fatigue (n=4/12) and nausea (n=2/12).
Both S-1 and capecitabine are orally available fluoropyrimidine. When combined with oxaliplatin, both S-1 and capecitabine were found to be equally active and well tolerated in advanced gastric cancer patients. As S-1 is not yet widely available worldwide, the combination of capecitabine and a platinum chemotherapy is still one of the most commonly adopted chemotherapy regimen for patients with advanced gastric cancer. In this study, we intend to assess the efficacy and feasibility of combining weekly i.p. paclitaxel with oxaliplatin and capecitabine.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer
Keywords
Advanced gastric cancer, unresectable gastric cancer, recurrent gastric cancer, with peritoneal metastasis, cancer cells on peritoneal cytology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IP Paclitaxel
Arm Type
Experimental
Arm Description
Paclitaxel will be administered intraperitoneally at 40mg/m2 on Days 1 and 8 in a 21-day cycle in patients receiving intravenous oxaliplatin 100mg/m2 on Day 1 and capecitabine 1000mg/m2 twice daily on Days 1-14.
Intervention Type
Drug
Intervention Name(s)
IP Paclitaxel
Intervention Description
Each treatment cycle will consist of 21 days, with 14 days on treatment and 7 days off-treatment. Oxaliplatin will be administered intravenously (on Day 1 of each cycle). Paclitaxel will be administered intra-abdominally on Day 1 and Day 8 of each cycle. In particular, a needle will be inserted into the intraperitoneal injection port for normal saline to be injected intra-abdominally over one hour, followed by paclitaxel chemotherapy over a further one hour. Capecitabine will be taken by mouth from Day 1 to 14 of each cycle.
Primary Outcome Measure Information:
Title
Overall survival (OS) rate
Description
The primary end point is 1-year survival because most patients may not have measurable disease, hence response rate and progression free survival are less easy to assess.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Number of participants with adverse events
Description
Toxicity will be monitored 3-weekly and graded according to the National Cancer Institute -Common Terminology Criteria for Adverse Events version 4.0.
Time Frame
3-weekly
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically proven unresectable or recurrent adenocarcinoma of stomach and gastroesophageal junction
Patients without prior systemic treatment. Patients who completed postoperative adjuvant chemotherapy (and radiotherapy) more than 180 days before may be enrolled
Peritoneal metastasis and/or cancer cells on peritoneal cytology
Age >21 years
Eastern Cooperative Oncology Group performance status 0-2
Adequate bone marrow function (neutrophil count >1500/mm3, hemoglobin >8.0 g/dl and platelet count >100 000/mm3)
Adequate liver function (bilirubin, AST (aspartate aminotransferase)/ALT (alanine aminotransferase) within upper limit of normal)
Adequate renal function (serum creatinine within the upper limit of normal)
Expected survival >3 months
Able to take orally
Able to understand and the willingness to sign a written informed consent document
The effects of proposed regimen on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because antitumor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Exclusion Criteria:
Metastasis to distant organ sites (such as the liver, lungs or bone)
When trastuzumab is considered for palliative chemotherapy
Known allergy to taxane, fluoropyrimidine or oxaliplatin
Previous malignancy other than gastric cancer diagnosed in the last 5 years except for basal cell carcinoma of skin or preinvasive cancer of cervix
Patients with reproductive potential who refuse to use an adequate means of contraception (including male patients)
Significant disease or conditions which, in the investigator's opinion, would exclude patient from the study
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or lactating female
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Peng Yong, MBBS
Phone
(65) 6779 5555
Email
Wei_Peng_Yong@nuhs.edu.sg
First Name & Middle Initial & Last Name or Official Title & Degree
Robert Lim, MBBS
Phone
(65) 6779 5555
Email
Robert_Lim@nuhs.edu.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei Peng Yong, MBBS
Organizational Affiliation
National University Hospital, Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
National University Hospital
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Peng Yong, MBBS
Phone
(65) 6779 5555
Email
Wei_Peng_Yong@nuhs.edu.sg
First Name & Middle Initial & Last Name & Degree
Maricel Cordero
Phone
(65) 6772 2612
Email
tiemsim_maricel_cordero@nuhs.edu.sg
First Name & Middle Initial & Last Name & Degree
Wei Peng Yong, MBBS
12. IPD Sharing Statement
Citations:
Citation
Ishigami H, Kaisaki S, Yamaguchi H et al. Phase I study of weekly intraperitoneal paclitaxel combined with S-1 and oxaliplatin for gastric cancer with peritoneal metastasis. J Clin Oncol 30, 2012 (suppl 4; abstr 146)
Results Reference
background
PubMed Identifier
22243774
Citation
Kim GM, Jeung HC, Rha SY, Kim HS, Jung I, Nam BH, Lee KH, Chung HC. A randomized phase II trial of S-1-oxaliplatin versus capecitabine-oxaliplatin in advanced gastric cancer. Eur J Cancer. 2012 Mar;48(4):518-26. doi: 10.1016/j.ejca.2011.12.017. Epub 2012 Jan 12.
Results Reference
background
PubMed Identifier
19605503
Citation
Ishigami H, Kitayama J, Kaisaki S, Hidemura A, Kato M, Otani K, Kamei T, Soma D, Miyato H, Yamashita H, Nagawa H. Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis. Ann Oncol. 2010 Jan;21(1):67-70. doi: 10.1093/annonc/mdp260. Epub 2009 Jul 15.
Results Reference
background
PubMed Identifier
36192514
Citation
Chia DKA, Ang JJ, Sundar R, Kim G, Shabbir A, So JBY, Yong WP. ASO Author Reflections: Combination Intra-Peritoneal and Systemic Chemotherapy for Gastric Cancer with Peritoneal Metastases. Ann Surg Oncol. 2022 Dec;29(13):8606-8607. doi: 10.1245/s10434-022-12102-1. Epub 2022 Oct 3. No abstract available.
Results Reference
derived
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Feasibility Study of Intraperitoneal Paclitaxel
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